Fig. 5
Effect of CB-839 on glutamine metabolism in MAS98.06 and MAS98.12 PDX tumors. a Average 13C NMR spectra (173.5-185.5 ppm and 75-13 ppm) for CB-839-treated and untreated MAS98.06 (blue) and MAS98.12 (red) tumors receiving 13C-labeled glutamine. The contribution to the average from each individual NMR spectrum is scaled to the sample mass. b Quantified amounts of selected 13C-labeled metabolites in each experimental group: 13C glutamine ([5-13C] Gln), glutamate to glutamine ratio ([5-13C] Glu/[5-13C] Gln), alanine ([1-13C] Ala), and proline ([5-13C] Pro) in the experimental groups. c MAS98.06 tumors take up and store glutamine (Gln) and use glutamine to produce glutamate (Glu), proline (Pro), alanine (Ala), lactate (Lac), and glutamate (Glu) through one turn in TCA cycle, as indicated by the filled blue circles (gray circle for Lac, only borderline significant). CB-839 causes an accumulation of Gln (arrow up) and reduced amounts of Pro, Al, and Glu (arrows down) in the tumors (only [1-13C] Glu, which is created after one turn in TCA cycle, is reduced). MAS98.12 tumors use glutamine (Gln) to produce Glu, Lac, and Ala as indicated by filled pink circles (gray circle for Ala, only borderline significant). CB-839 causes accumulation of Gln in MAS98.12 tumors, but does not significantly change the amount of any other 13C-enriched metabolites *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001